The cyclic redox dye Azure B as a novel cyanide antidote: in vivo efficacy studies

项目摘要/摘要 从我们最近的实验中获得的数据支持这一观点，这些数据是由父母拨款资助的 亚甲基蓝的单脱甲基代谢物天青B(Azb)是一种非常有效的氰化物(CN)。 解药。AZB耐受性很好，在低剂量时表现出比MB更高的疗效。 CN仍然是儿童的一个主要公共卫生问题，这是一个被严重忽视的问题。 例如，目前还没有研究评估这种药物在儿科人群中的安全性或有效性。 亚硝酸盐化合物或羟钴胺，是目前成人使用的两种主要的CN解毒剂。然而，孩子们可以是， 像成年人一样，在吸入烟雾的过程中醉酒。在发展中国家，儿童接触CN往往会导致 摄入含有CN的农产品--如杏仁或木薯。发展中的 幼儿急性氰化物中毒的后果必须考虑到心脏的脆弱性 而脑组织对细胞的“缺氧”产生CN。然而，目前还没有系统的正在进行的研究 治疗暴露于急性CN中毒后果的儿童。 在本行政副刊中提出的为期一年的提案的目的是确定 AZB对口服致死剂量CN的幼鼠有效，可防止死亡并改善 大体结果。一种致死性CN口服中毒模型将用于20日龄大鼠，无论性别；Azb将 当动物处于昏迷状态时，在摄入CN后，以不同的剂量给予。

PROJECT SUMMARY/ABSTRACT The data obtained from our recent experiments, which were funded by the parent grant, support the view that the mono-demethylated metabolite of methylene blue, Azure B (AzB), is a very effective cyanide (CN) antidote. AzB is very well tolerated, while displaying a higher efficacy than MB at low doses. CN still represents a major public health problem in children, a question that has been greatly overlooked. For instance, there have been no studies evaluating the safety or even the efficacy in the pediatric population of nitrite compounds or hydroxocobalamin, the two main CN antidotes currently used in adult. Yet, children can be, like adults, intoxicated during smoke inhalation. In developing countries, exposure of children to CN often result from the ingestion of CN containing produces – such as apricot kernels or cassava. The developmental consequences of an acute CN intoxication in a young child must take into account the vulnerability of the heart and the brain to the cellular “anoxia” produced by CN. Yet, there is no structured on-going research on the treatment of children exposed to the consequences of an acute CN intoxication. The one-year proposal developed in this administrative supplement has the objective of establishing that AzB is effective in juvenile rats following oral ingestion of a lethal dose of CN, preventing death and improving the general outcome. A model of lethal CN oral intoxication will be used in 20-day old rats of either sex; AzB will be administered at different dosages, after ingestion of CN, when the animals are in a coma.